Hydrolysis of nerve agents by model nucleophiles: A computational study

Department of Chemistry, The Ohio State University, 100 W. 18th Avenue, Columbus, OH 43210, USA.
Chemico-Biological Interactions (Impact Factor: 2.58). 06/2008; 175(1-3):200-3. DOI: 10.1016/j.cbi.2008.04.026
Source: PubMed


Density functional theory calculations were employed to study the reaction of five nerve agents with model nucleophiles, including EtX(-) and EtXH (X=O, S, Se) for serine, cysteine and selenocysteine, respectively. Calculations at the B3LYP/6-311++G(2d,p) level of theory predict an exothermic reaction between ethoxide and all of the nerve agents studied. As compared to EtO(-) as a nucleophile, these reactions become approximately 30 kcal/mol more endothermic for EtS(-), and by approximately 40 kcal/mol for EtSe(-). The equivalent reactions with the neutral nucleophiles (EtXH) were more endothermic. The effect of solvation on the reaction thermochemistry was determined using a polarizable continuum model simulating the dielectric constant of chloroform. While there was a large exothermic shift for reactions involving charged nucleophiles with solvation modeling, the corresponding shift was minimal for the reaction with neutral nucleophiles.

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